A research program is proposed dealing with several aspects of the metabolism and transport of vitamin A and vitamin D. This program seeks to acquire detailed and fundamental information about the metabolism of these fat-soluble vitamins and to apply this information where possible to the study of human biology and disease. Four major projects are proposed. Project One, on vitamin A transport and retinol-binding protein (RBP) metabolism, will aim to examine the plasma vitamin A transport system in detail, with the goal of defining the cellular and molecular mechanisms involved in the regulation of RBP production and secretion by the liver. Chemical studies of the vitamin A transport system will be continued. Project Two will aim to characterize the enzymatic hydrolysis of retinyl esters in rat liver and to explore the metabolic regulation of retinyl ester hydrolase activity in liver. The possible coordination between retinyl ester hydrolysis and RBP production and secretion will be studied. Project Three will aim to examine the intracellular binding proteins for retinol and for retinoic acid in detail. Studies are proposed to isolate and characterize these intracellular binding proteins, to explore their tissue distribution and metabolic regulation, and to examine their possible physiologic roles. Project Four aims to examine in detail the specific protein responsible for the transport of vitamin D and 25-hydroxyvitamin D in human plasma. The goals of this project are to characterize the chemical structure of this transport protein, to explore in detail its interaction with various vitamin D-related steroids, and to study the effects of various clinical disorders on the plasma levels and on the turnover and metabolism of the protein.